Cancer Science

The inhibitory immune checkpoint ILT2 is highly expressed in glioblastoma. Its blockade partially restores antitumor responses in this tumor and combination with temozolomide enhances this anti-glioblastoma effect.

Resveratrol was identified as the most effective compound for chemoprevention against colorectal adenoma comprehensively from 1309 FDA-approved compounds using connectivity map analysis and in vitro screening of patient-derived organoids of colorectal adenoma. Resveratrol effectively inhibited development of colorectal adenoma in Apc-deficient mice and in chemically carcinogenesis rat models by suppressing the expression of LEF1 in the Wnt signaling pathway.

Our study suggests that TIMP1 is overexpressed in the right-sided colorectal cancer, and promotes cell proliferation and invasion capability through TIMP1/FAK/Akt pathway, leading to poor prognosis.

We recently reported that HMGB1 showed a negative impact on anti-tumor immunity, however, a positive role of HMGB1 in the initiation of innate and subsequent adaptive immunity has also been shown. In this study, we found that the suppression of HMGB1 in the tumor microenvironment does not inhibit the induction of neoantigen-specific immunity.

F-actin bundling was modulated by the extracellular matrix through biomechanical forces via the receptor integrin β1, contributing to the release of E3 ligase Tripartite motif protein 11 (TRIM11) from the cytoskeleton and to the degradation of the glycolytic rate-limiting enzyme phosphofructokinase (PFK). Inhibiting PFK contributed to enhanced glycolysis and upregulation of hypoxia-inducible factor 1 (HIF1α), thereby reprogramming stem cell transcription factors and facilitating the dedifferentiation of colorectal cancer cells.

EZH1 depletion in MYCN-amplified neuroblastoma cells resulted in significant cell death as well as xenograft inhibition. TYMS and POLA2 were transcriptionally activated by MYCN and EZH1-related epigenetic modification. EZH inhibitor UNC1999 treatment significantly sensitized MYCN-amplified neuroblastoma cells to 5-FU treatment.

CARTITUDE-1, a phase 1b and 2 open-label study of ciltacabtageneautoleucel (cilta-cel) in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), had a protocol-specified separate Japanese cohort to characterize cilta-cel efficacy and safety in Japanese patients. All eight of eight patients responded, yielding an  overall response rate of 100% and safety was manageable and comparable to the main cohort. A positive benefit/risk profile for cilta-cel was established for heavily pretreated Japanese patients with RRMM.

EIF3B is a promotor in malignant melanoma, and the role of driver played by EIF3B is mediated by PTGS2. Silencing PTGS2 could reverse the promotion effect caused by overexpression of EIF3B. EIF3B was identified as a potential therapeutic target for malignant melanoma.

Conventional CAR-T cells combat cancers on their own and rarely induce sufficient effects against solid tumors. In contrast, administration of 7×19 CAR-T cells induces infiltration and proliferation of not only CAR-T cells but also T cells and dendritic cells of the recipient in the tumor tissue. Epitope-spreading is induced by the interaction of the infiltrating cells, resulting in synergistic anti-tumor effects.

Chimeric antigen receptor (CAR)-engineered T cell therapy is an emerging therapeutic that can cure refractory cancer. Understanding T cell properties at the molecular level would enable us to improve its efficacy further. This manuscript focuses on epigenetic profiles associated with antitumor T cell functions and thoroughly reviews how epigenetic modification can be applied in cancer immunotherapy.

CD96⁺ cells infiltration represented an independent adverse prognosticator and could predict prognosis of adjuvant chemotherapy and therapeutic responsiveness to PD-1 inhibitor. Immunosuppression by CD96 level was characterized by exhausted CD8⁺ T cells.

We demonstrate that DDR1 promotes colorectal tumor growth only in vivo. Mechanistically, DDR1 is a negative immunomodulator in colorectal cancer and involved in low infiltration of CD4 + and CD8 + T cells by inhibiting IL-18 synthesis. We also report that DDR1 enhances the expression of PD-L1 through activating JNK/c-Jun pathway.

We found that metformin inhibited the NF-kB signaling pathway via downregulating TRIM37. Metformin inhibited the ubiquitination of TRAF2 induced by TRIM37-overexpression.

Ferrocene-containing redox phospholipid polymers induce immunogenic cell death (ICD), followed by the release of damage-associated molecular patterns in murine colon cancer CT26 cells via the extraction of intracellular electrons. Injection of pMFc-treated CT26 cells successfully inhibited tumorigenesis against subsequent challenge, indicating that the redox phospholipid polymers elicit anti-tumor immunity via the induction of ICD.

Lack of molecular target is a tricky problem in osteosarcoma treatment. In this study, we report (1) high frequency of GPC3 detection (73.77%; 45/61) and its overlapped expression with CD133 in OSs; (2) successful generation of patient-derived organoids (PDOs) from 24 human osteosarcoma cases (OSs) as ex vivo experimental model; (3) the effectiveness of anti-GPC3 strategy against GPC3-expressing OS PDOs and PDXs, accompanied with suppressed Wnt/β-catenin signaling. We therefor propose that GPC3 would be a promising target for personalized OS therapy.

1. MYO10 knockout reduced CRC cell proliferation, invasion, and migration in vitro, and CRC metastasis in vivo. 2. We identified RACK1 by LC-MS/MS and demonstrated that MYO10 interacts with and stabilizes RACK1. 3. MYO10 promotes CRC cell progression and metastasis via ubiquitination-mediated RACK1 degradation and integrin/Src/FAK signaling activation.

we reported that USP28 promotes the activity of the Wnt signaling pathway through maintaining the stability of TCF7L2. We further showed that FBXW7 is the E3 ubiquitinatin ligase for TCF7L2. By regulating the levels of TCF7L2, USP28 modulates the Wnt/β-catenin signaling pathway in liver cancer. As a result, liver cancer cells are sensitive to USP28 depletion or inhibition by a small molecule inhibitor. Our results suggest that USP28 could be a potential therapeutic target for liver cancer.

As the core molecule in the SRGS, knocking down the KIR2DL4 of human NK cells in vitro can inhibit the cytotoxicity of NK cells, and can also inhibit the secretion of tumor necrosis factor-α and interferon-γ by NK cells. On the contrary, up-regulation of KIR2DL4 can activate MEK/ERK signaling pathway, which is the activation pathway of NK cells. Our senescence scoring system (SRGS) and nomogram model can accurately stratify the risk of CM patients and effectively predict the effect of immunotherapy and prognosis in CM patients.